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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
other: NF EN ISO 10993-10 (February 2003) concerning biological evaluation of medical devices: Tests for irritation and delayed-type hypersensitivity
Deviations:
no
Principles of method if other than guideline:
Buehler test selected for sensitisation testing because substance was thought to have (slight) irritating properties by that time
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
An appropriate guinea pig maximisation test/Buehler test is available which would not justify conducting an additional LLNA due to animal welfare. Also according to“Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint-specific guidance” (ECHA, 2008) any OECD method can be used for registration.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name Slag, ferrous metal, blast furnace (air cooled - ABS), fine-ground
Batch no P2009 01862
Appearance solid
Composition UVCB
Molecular formula not applicable (UVCB)
Molecular weight not applicable (UVCB
Purity 100 w/w % slag
Homogeneity not stated
Volatility extremely low (melting point > 300 °C)
Stability solid slag is stable at room temperature
Solubility slightly soluble in water
Date of production not stated
Date of expiry Year 2024
Storage conditions Room temperature 20 ± 5°C

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
Male albino guinea pigs were supplied by CHARLES RIVER (F-69592 L’ARBRESLE). The animals were identified individually by marking with picric acid and a tattoo placed on their ear. They weighed between 252 g and 295 g at the beginning of the main test and were 4 weeks old. The animals were adapted to the test conditions for at least 5 days with the drinking water (tap water) and food were supplied ad libitum, under stabling and nutritional conditions identical to those of the test.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
The slag leachate was prepared according to DIN 38414-4 DEV-S4 (L/S 10/1) and had a nominal concentration of 100 g/L .
pH was between 7.26 and 8.56
The test extracts have been prepared at the following dates:
08 September 2009 to 09 September 2009 (pH=7.26, 22°C, colourless solution)
15 September 2009 to 16 September 2009 (pH=7.24, colourless solution)
21 September 2009 to 22 September 2009 (pH=8.56, colourless solution)
28 September 2009 to 29 September 2009 (pH=8.02, 22°C, colourless solution)
13 October 2009 to 14 October 2009 (pH=8.08, colourless solution)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
The slag leachate was prepared according to DIN 38414-4 DEV-S4 (L/S 10/1) and had a nominal concentration of 100 g/L .
pH was between 7.26 and 8.56
The test extracts have been prepared at the following dates:
08 September 2009 to 09 September 2009 (pH=7.26, 22°C, colourless solution)
15 September 2009 to 16 September 2009 (pH=7.24, colourless solution)
21 September 2009 to 22 September 2009 (pH=8.56, colourless solution)
28 September 2009 to 29 September 2009 (pH=8.02, 22°C, colourless solution)
13 October 2009 to 14 October 2009 (pH=8.08, colourless solution)
No. of animals per dose:
11 controls (including 3 positive controls)
21 test animlas in total
Details on study design:
Before each test extract application, the animals were carefully shorn before each test extract application:
- On the inter-scapular zone for the induction phase
- On the dorso-lumbar zone for the challenge phase
At least 3 h before the first reading (challenge phase) they were shorn a second time.
The animals were weighed at the beginning and at the end of the study.
Challenge controls:
3 males with the eference substance: α-Hexylcinnamaldehyde CAS n° 101-86-0
Positive control substance(s):
yes
Remarks:
α-Hexylcinnamaldehyde

Results and discussion

Positive control results:
the positive control is a sensitizer with 9-100 % of animals developing positive response

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
11
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 11.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
11
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 11.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100 g/L
No. with + reactions:
0
Total no. in group:
21
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 g/L. No with. + reactions: 0.0. Total no. in groups: 21.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100 g/L
No. with + reactions:
0
Total no. in group:
21
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 g/L. No with. + reactions: 0.0. Total no. in groups: 21.0. Clinical observations: none.

Any other information on results incl. tables

No abnormalities and no differences in the body weight between the control and the treated group, no mortality, and no clinical signs

were observed in any group.

Individual results of macroscopic evaluation (readings at 24 and 48 hours) of cutaneous reactions

Animal no. controls

100% (MNIC)

24 h Er

100% (MNIC)24 h Oe

100% (MNIC) 48 hEr

100% (MNIC) 48 hOe

50% (1/2 MNIC) 24 hEr

50% (1/2 MNIC)24 h  Oe

50% (1/2 MNIC) 48 hEr

50% (1/2 MNIC) 48 hOe

2206

0

0

0

0

0

0

0

0

2207

0

0

0

0

0

0

0

0

2208

0

0

0

0

0

0

0

0

2209

0

0

0

0

0

0

0

0

2210

0

0

0

0

0

0

0

0

2211

0

0

0

0

0

0

0

0

2212

0

0

0

0

0

0

0

0

2213

0

0

0

0

0

0

0

0

2214

0

0

0

0

0

0

0

0

2215

0

0

0

0

0

0

0

0

2216

0

0

0

0

0

0

0

0

Treated Group

Animal no. treated

100% (MNIC)

24 h Er

100% (MNIC)24 h Oe

100% (MNIC) 48 hEr

100% (MNIC) 48 hOe

50% (1/2 MNIC) 24 hEr

50% (1/2 MNIC)24 h  Oe

50% (1/2 MNIC) 48 hEr

50% (1/2 MNIC) 48 hOe

2217

0

0

0

0

0

0

0

0

2218

0

0

0

0

0

0

0

0

2219

0

0

0

0

0

0

0

0

2220

0

0

0

0

0

0

0

0

2221

0

0

0

0

0

0

0

0

2222

0

0

0

0

0

0

0

0

2223

0

0

0

0

0

0

0

0

2224

0

0

0

0

0

0

0

0

2225

0

0

0

0

0

0

0

0

2226

0

0

0

0

0

0

0

0

2227

0

0

0

0

0

0

0

0

2228

0

0

0

0

0

0

0

0

2229

0

0

0

0

0

0

0

0

2230

0

0

0

0

0

0

0

0

2231

0

0

0

0

0

0

0

0

2232

0

0

0

0

0

0

0

0

2233

0

0

0

0

0

0

0

0

2234

0

0

0

0

0

0

0

0

2235

0

0

0

0

0

0

0

0

2236

0

0

0

0

0

0

0

0

2237

0

0

0

0

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
ABS: not irritating and not sensitising
Executive summary:

The possible allergenic activity of slag, ferrous metal, blast furnace (air cooled - ABS), granular (8-11 mm) was tested according to OECD 406 and NF EN ISO 10993-10 (February 2003) concerning biological evaluation of medical devices: Tests for irritation and delayed-type hypersensitivity.

Slag leachate was prepared by DIN 38414 -4 DEV S-4 by leaching for 24 h at a liquid/solid ratio of 10/1. For induction, 21 Guinea pigs were exposed to the leachate in triplicate topical applications under occlusive dressing for 6 h at 100 % (undiluted) leachate. After a 14-day rest phase, the challenge phase consisted of a single topical application (24 h) of the leachate at 100 % and 50 % dilution in demineralised water.

No visible cutaneous reactions and no intolerance reaction was recorded in the challenge phase neither at 100 % nor at 50 %, and no reaction was recorded in the negative controls.

Slags, ferrous metal, blast furnace are not irritating and do not need to be classified as a skin sensitizer. No signal word and no hazard statement is required.